African swine fever virus assembles a single membrane derived from rupture of the endoplasmic reticulum

Collective evidence argues that two members of the nucleocytoplasmic large DNA viruses (NCLDVs) acquire their membrane from open membrane intermediates, postulated to be derived from membrane rupture. We now study membrane acquisition of the NCLDV African swine fever virus. By electron tomography (ET), the virion assembles a single bilayer, derived from open membrane precursors that collect as ribbons in the cytoplasm. Biochemically, lumenal endoplasmic reticulum (ER) proteins are released into the cytosol, arguing that the open intermediates are ruptured ER membranes. ET shows that viral capsid assembles on the convex side of the open viral membrane to shape it into an icosahedron. The viral capsid is composed of tiny spikes with a diameter of ∼5nm, connected to the membrane by a 6nm wide structure displaying thin striations, as observed by several complementary electron microscopy imaging methods. Immature particles display an opening that closes after uptake of the viral genome and core proteins, followed by the formation of the mature virion. Together with our previous data, this study shows a common principle of NCLDVs to build a single internal envelope from open membrane intermediates. Our data now provide biochemical evidence that these open intermediates result from rupture of a cellular membrane, the ER. © 2015 John WileyDeutsche Forschungsgemeinschaft personal grant KR2173 to Jacomine Krijnse Locker. German Andres is supported by the ‘Amarouto Program for senior scientists from the Comunidad Autónoma de Madrid’ and by grants BFU2009-08085 and AGL2013-48998-C2- 2-R from the Spanish Ministerio de Economía y CompetitividadPeer Reviewe

Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

Background: This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia.Methods: We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).Results: In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.Conclusion: In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings

Using the European Language Grid as a consumer

This chapter describes the European Language Grid cloud platform from the point of view of a consumer who wishes to access language resources or make use of language technology tools and services. Three aspects are discussed: 1. the webbased user interface (UI) for casual and non-technical users, 2. the underlying REST APIs that drive the UI but can also be called directly by third parties to integrate ELG functionality in their own tools, and 3. the Python Software Development Kit (SDK) that we have developed to simplify access to these APIs from Python code. The chapter concludes with a preview of the upcoming payment module that will enable the sale of commercial LT services and resources through ELG, and a discussion of how ELG compares and relates to other similar platforms and initiatives

The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing APOE3, but not APOE4, animals with dietary n-3 PUFA decreased bodyweight gain, plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings demonstrate that an APOE3 genotype predisposes mice to develop obesity and its metabolic complications, which was attenuated by n-3 PUFA supplementation.—Slim, K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

Recruitment and retention of participants from socioeconomically deprived communities : lessons from the Awareness and Beliefs About Cancer (ABACus3) randomised controlled trial

Background Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample. Methods Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections. Results The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n = 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n = 212) retention at 2-weeks and 85% (n = 199) at 6-months. Community settings yielded 75% (n = 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n = 148) were female, with 66% (n = 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings. Conclusions The ABACus3 trial achieved recruitment and high retention with a population that is often “hard to reach” or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement. This study adheres to CONSORT guidelines. Trial registration Retrospectively registered with ISRCTN (http://www.isrctn.com/ISRCTN16872545) on 12.01.2018